Pentoxifylline: A Useful Adjuvant in the Critically Ill?

Abstract

Sepsis and the systemic inflammatory response syndrome (SIRS) represent an extremely complex biochemical and pathophysiological disorder which still lacks specific effective pharmacological intervention. Infection, trauma, major surgery (e.g., cardiac surgery) or critical illness initiate an inflammatory cascade, which leads to an activation of various regulatory mechanisms. There is a large body of literature implicating that the inflammatory process is initiated and/or maintained by interactions of circulating leukocytes with the endothelium via cell, and organ-specific, adhesion molecules [1–3]. Neutrophils are essential for bacterial killing in infectious disease, but they also are able to injure the host tissue. Neutrophil ‘rolling’ along the endothelium initiates a cascade of cellular interactions resulting in endothelial damage (e.g., capillary leakage) and subsequent development of (multiple) organ damage [3]. ‘Rolling’ is defined as deceleration and attachment of neutrophils to the luminal surface of the vascular endothelium. Intercellular adhesion and adhesion to endothelial cells are necessary for the arrest of circulating leukocytes and transendothelial migration [3, 4]. The process of ‘rolling’, firm adhesion, emigration, and migration in the interstitial space are mediated by adhesion molecules expressed on both the endothelial and the leukocyte surface. Three main families of adhesion molecules have been identified [4, 5]: